Cryotherapy method for detecting and treating vulnerable plaque

ABSTRACT

Methods, apparatus, and kits detect and/or treat vulnerable plaque of a blood vessel. A temperature differential can be sensed along a lumen surface with temperature sensors on a balloon filled with warm gas. Treatment methods include controlled and safe cryogenic cooling of vulnerable plaque to inhibit release of retained fluid within the vulnerable plaque so as to inhibit acute coronary syndrome and to help maintain patency of a body lumen.

CROSS-REFERENCE TO RELATED APPLICATION

This application is a continuation of U.S. patent application Ser. No.11/228,691 filed Sep. 16, 2005, which is a divisional patent applicationwhich claims priority from U.S. patent application Ser. No. 10/387,347filed on Mar. 11, 2003, now U.S. Pat. No. 6,955,174, which is acontinuation-in-part of U.S. patent application Ser. No. 09/641,462filed Aug. 18, 2000, the full disclosures of which are incorporatedherein by reference.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates generally to methods, apparatus, and kitsfor treating blood vessels. More particularly, the present inventionprovides methods, apparatus, and kits for identifying and/or treating alesion. In one exemplary embodiment, the invention provides deviceswhich are particularly useful for identification and treatment ofvulnerable atherosclerotic plaque within a patient's vasculature toinhibit harmful releases within the vasculature, such as those which maybe responsible for strokes or acute coronary syndromes of unstableangina, myocardial infarction, and sudden cardiac death.

Atherosclerotic plaque is present to some degree in most adults. Plaquescan severely limit the blood flow through a blood vessel by narrowingthe open vessel lumen. This narrowing effect or stenosis is oftenresponsible for ischemic heart disease. Fortunately, a number ofpercutaneous intravascular procedures have been developed for treatingatherosclerotic plaque in a patient's vasculature. The most successfulof these treatments may be percutaneous transluminal angioplasty (PTA).PTA employs a catheter having an expansible distal end, usually in theform of an inflatable balloon, to dilate a stenotic region in thevasculature to restore adequate blood flow beyond the stenosis. Otherprocedures for opening stenotic regions include directional atherectomy,laser angioplasty, stents, and the like. Used alone or in combination,these percutaneous intravascular procedures have provided significantbenefits for treatment of stenosis caused by plaque.

While treatments of stenosis have advanced significantly over the lastfew decades, the morbidity and mortality associated with vascularplaques have remained significant. Recent work suggests that plaque maygenerally fall into one of two different general types: standardstenotic plaques and vulnerable plaques. Stenotic plaque, which issometimes referred to as thrombosis-resistant plaque, can generally betreated effectively by the known intravascular lumen opening techniquesmentioned above. Although the stenosis they induce may benefit fromtreatment, these atherosclerotic plaques themselves are often a benignand effectively treatable disease.

Unfortunately, as plaque matures, narrowing of a blood vessel by aproliferation of smooth muscle cells, matrix synthesis, and lipidaccumulation may result in formation of a plaque which is quitedifferent than a standard stenotic plaque. Such atherosclerotic plaqueoften becomes thrombosis-prone, and can be highly dangerous. Thisthrombosis-prone or vulnerable plaque may be a frequent cause of acutecoronary syndromes.

The characterization of these vulnerable (and potentiallylife-threatening) plaques is currently under investigation. A number ofstrategies have been proposed to detect a vulnerable plaque. Proposedstrategies include angiography, intravascular ultrasound, angioscopy,magnetic resonance imaging, magnetic resonance diffusion imaging,spectroscopy, infrared spectroscopy, scintigraphy, optical coherencetomography, electron beam computed tomographic scanning, andthermography, all of which have had limited success. In particular,proposed thermography methods detect temperature variations, asvulnerable plaque is typically inflamed and as such gives off more heatthan standard stenotic plaque. While current thermography methods showpromise, they continue to suffer from limited temperature sensitivitywhich may often result in inaccurate detections of vulnerable plaque.

While the known procedures for treating plaque have gained wideacceptance and shown good efficacy for treatment of standard stenoticplaques, they may be ineffective (and possibly dangerous) whenthrombotic conditions are superimposed on atherosclerotic plaques.Specifically, mechanical stresses caused by primary treatments like PTAor stenting may actually trigger release of fluids and/or solids from avulnerable plaque into the blood stream, thereby potentially causing acoronary thrombotic occlusion.

For these reasons, it would be desirable to provide methods, apparatus,and kits for the detection and treatment of vulnerable plaque in bloodvessels. The methods and apparatus should be suitable for intravascularand intraluminal introduction, preferably via a percutaneous approach.It would be particularly desirable if the new methods and apparatus wereable to detect the vulnerable plaque accurately and/or deliver thetreatment in a very controlled and safe manner, with minimal deleteriouseffects on adjacent tissues. Treatment methods, apparatus, and kitsshould further be effective in inhibiting release of the vulnerableplaque with minimum side effects. At least some of these objectives willbe met by the invention described herein.

2. Description of the Background Art

A cryoplasty device and method are described in PCT Publication No. WO98/38934. Balloon catheters for intravascular cooling or heating apatient are described in U.S. Pat. No. 5,486,208 and WO 91/05528. Acryosurgical probe with an inflatable bladder for performingintrauterine ablation is described in U.S. Pat. No.5,501,681.Cryosurgical probes relying on Joule-Thomson cooling aredescribed in U.S. Pat. Nos. 5,275,595; 5,190,539; 5,147,355; 5,078,713;and 3,901,241.Catheters with heated balloons for post-angioplasty andother treatments are described in U.S. Pat. Nos. 5,196,024; 5,191,883;5,151,100; 5,106,360; 5,092,841; 5,041,089; 5,019,075; and 4,754,752.Cryogenic fluid sources are described in U.S. Patent Nos. 5,644,502;5,617,739; and 4,336,691. The following U.S. Patents may also berelevant to the present invention: U.S. Pat. Nos.5,458,612; 5,545,195;and 5,733,280.

Thermography is described by Ward Casscells, et al. in The VulnerableAtherosclerotic Plaque: Understanding. Identification, and Modification,Chpt. 13, pp. 231-242 (1999); and in L. Diamantopoulos, et al. at thefollowing Internet address:http://www.eurekalert.org/releases/ahaati041499.html. The impact of lowtemperatures on lipid membranes is described by Jack Kruuv in an articleentitled Advances in Molecular and Cell biology, vol. 19, pp. 143-192(1997); P. J. Quinn in Cryobiology. Vol. 22, pp. 128-146 (1985); andMichael J. Taylor, Ph.D. in Biology Of Cell Survival In The Cold,(Harwood Academic Publishers, In Press).

The full disclosures of each of the above references are incorporatedherein by reference.

SUMMARY OF THE INVENTION

The present invention provides detection and treatment of vulnerableplaque within a blood vessel of a patient. The blood vessel may be anyblood vessel in the patient's vasculature, including veins, arteries,and particularly coronary arteries. The vessel will typically bepartially stenosed, at least in part from vulnerable plaque. Inparticular, the present invention may inhibit release of retained fluidwithin the vulnerable plaque so as to inhibit acute coronary syndromeand to help maintain the patency of a body lumen. The present inventionmay also provide for the treatment of vulnerable plaque in carotidarteries for stroke prevention. Where the patient's vasculature has boththe vulnerable plaque and standard stenotic plaque, the treatmenttechniques described herein may be selectively directed to thevulnerable plaque, optionally without substantial cooling of thestandard stenotic plaque. In other embodiments, both types of plaque maybe treated.

In a first aspect, the present invention provides a method for treatingvulnerable plaque of a blood vessel. The method comprises cooling thevulnerable plaque to a temperature sufficient to inhibit release ofretained fluid from within the vulnerable plaque into the blood stream.The cooling treatment will often be directed against all or a portion ofa circumferential surface of a lumen of the blood vessel, and willpreferably inhibit release of lipid-rich liquid being releasablyretained by the vulnerable plaque.

Optionally, a portion of the vasculature may be identified in whichreleasing of the retained fluid should be inhibited. For example,releasing of the retained fluid from a vulnerable plaque in some cardiacarteries may result in sudden cardiac death. Releasing of the retainedfluid from a vulnerable plaque in the carotid arteries may result instroke. Hence, when it is determined that a plaque is located withinsuch a portion of the vasculature, the cooling step may be performed atthis identified plaque location. Optionally, such cooling may beperformed without specifically identifying the plaque as a vulnerableplaque. In other embodiments, the vulnerable plaque may bedifferentiated from standard stenotic plaque, often prior to initiationof the cooling. Hence, the cooling may be selectively directed atvulnerable plaque, rather than being applied to plaque in general.Advantageously, a single balloon catheter may be used to bothdifferentiate and treat the vulnerable plaque.

Differentiation of vulnerable plaque from standard stenotic plaque maybe enhanced by the use of a balloon catheter inflated with a gas. Thedifferentiation may be effected using a temperature sensor for sensing atemperature of a tissue adjacent the balloon. Surprisingly, plaquedifferentiation benefits from gas temperatures within the balloon ofabout 20° C. or more, preferably being 30° C. or more. Hence, theballoon may be inflated so that an initial temperature of the gas withinthe balloon is about 30° C. Inflation with such a warm gas can amplifythe measured temperature differences (for example) sensed by temperaturesensors distributed along a balloon wall and in thermal engagement withthe vulnerable plaque (at a first sensor) and a standard stenotic plaqueor healthy luminal wall (at a second sensor).

Cooling of the vessel may be effected by introducing a catheter into alumen of the blood vessel. A first balloon is positioned within thevessel lumen adjacent the vulnerable plaque. Cryogenic cooling fluid isintroduced into the first balloon and exhausted. A second balloondisposed over the first balloon is expanded to radially engage thevessel lumen. Generally, the temperature of an inside surface of thefirst balloon will be in the range from about −55° C. to −75° C. and anoutside surface of the first balloon will be in the range from about−25° C. to −45° C. The temperature of an outside surface of the secondballoon will be in the range from about 10° C. to −40° C., preferablyfrom about 10° C. to −20° C., more preferably from about 5° C. to −10°C. In alternative embodiments, the temperature of an inside surface ofthe first balloon may be in a range from about −30 C to 31 50 C, and anoutside surface of the first balloon may be in a range from about −20 Cto −40 C.

Usually, the temperature at the surface of the blood vessel lumen is inthe range from about 10° C. to −40° C., preferably from about 10° C. to−20° C., more preferably from about 5° C. to −10° C. The tissue istypically maintained at the desired temperature for a time period in therange from about 15 seconds to 120 seconds, preferably from 30 secondsto 60 seconds, optionally being in a range from about 20 seconds toabout 60 seconds. Vulnerable plaque stabilization may be enhanced byrepeating cooling in cycles, typically with from about 1 to 3 cycles,with the cycles being repeated at a rate of about one cycle every 120seconds.

Surprisingly, cooling temperatures above 0° C. can effect a transitionof the vulnerable plaque's lipid core from a disordered cystalline statefluid to a ordered crystalline state solid or gel. Thus, vulnerableplaque can be stabilized by cooling the lipid-rich liquid sufficientlyto change a state of the lipid-rich liquid, typically to a highlyordered hexagonal lattice at transition temperatures generally in therange from about 10° C. to −10° C. The stabilization may, at least inpart, remain in effect after subsequent return of the tissue to a normalbody temperature. The stabilization may, at least in part, betransitory, with the stabilization effect diminishing and/ordisappearing after cooling is terminated. The vulnerable plaque may betreated while it remains at least partially stabilized.

Advantageously, the cooling may be accurately controlled to tailor adesired tissue response. Cooling may be performed so as to causeapoptosis and/or necrosis in the tissues comprising or adjacent to thevulnerable plaque. Alternatively, the cooling may also be performed in amanner that avoids causing apoptosis and/or necrosis. Cooling maystabilize the vulnerable plaque while inhibiting necrosis and/orapoptosis of tissue adjacent the lipid-rich liquid, particularly of thetissues defining a cap of cells between the lipid-rich liquid and thelumen of the blood vessel. Cooling may also inhibit inflammation anddeterioration of the vulnerable plaque. The cooling treatment mayfurther inhibit rupture of the cap of cells of the vulnerable plaque.

In other aspects, the present invention of cooling the vulnerable plaqueto inhibit release of lipid-rich liquid may be combined with additionaltreatments. For example, one adjunctive method may comprise treating thecooled vulnerable plaque with a primary treatment. Suitable primarytreatments may include balloon angioplasty, atherectomy, rotationalatherectomy, laser angioplasty, or the like, where the lumen of thetreated blood vessel is enlarged to at least partially alleviate astenotic condition. The primary treatment may also include proceduresfor controlling restenosis, such as stent placement. In the case ofarteries, the primary treatment will be effected shortly before, during,or preferably very shortly after the cooling treatment, preferablywithin 60 seconds of the cooling treatment, more preferably immediatelyfollowing the cooling of the lipid-rich liquid to a desired temperature.Alternatively, cooling methods may additionally comprise passivating thevulnerable plaque by reducing a size of the lipid-rich liquid, changinga cellular consistency or composition of the lipid-rich liquid,enhancing a structural integrity of the cap (e.g. increasing a thicknessof the cap), modifying a cellular composition or structural propertiesof the cap, and/or the like by altering the chemistry or life cycle ofthe vulnerable plaque.

In another aspect, the present invention provides a method for treatingvulnerable plaque of a blood vessel, the vulnerable plaque releasablyretaining fluid. The method includes detecting the vulnerable plaquewith a balloon catheter and cooling the vulnerable plaque with theballoon catheter to a temperature sufficient to inhibit release of theretained fluid into the blood vessel.

Preferably, the detecting step will comprise inflating a balloon of theballoon catheter so that a gas within the balloon is at a temperature of30° C. or more. The cooling step may comprise cooling an outer surfaceof the balloon to a temperature of about 10° C. or less.

In another aspect, the present invention provides a method for detectingvulnerable plaque of a blood vessel. The method includes positioning aballoon within the vessel lumen adjacent a plaque. The balloon isinflated so that a plurality of temperature sensors affixed to theballoon are coupled to a surface of the vessel lumen. A temperaturedifferential along the lumen surface is sensed with the sensors.

The inflating step may be performed so that the gas within the balloonhas a temperature of about 20° C. or more, the balloon preferably beinginflated so that the gas has an initial temperature in the balloon of30° C. or more. Surprisingly, temperature sensors along the balloon wallcan detect a temperature differential of greater than about 1° C.between a vulnerable plaque and an adjacent portion of the luminal wallwith such a system. Additionally, the size of the “hot” region disposedalong the vessel wall may increase when the balloon is inflated with thegas. Hence, the use of a warm gas within a balloon catheter can act toamplify the sensitivity of the system for detection of vulnerableplaques.

In another aspect, the present invention provides a cryotherapy catheterfor detecting and treating vulnerable plaque of a blood vessel having alumen surface. The catheter generally comprises a catheter body having aproximal end and a distal end with a cooling fluid supply lumen and anexhaust lumen extending therebetween. A first balloon is disposed nearthe distal end of the catheter body in fluid communication with thesupply lumen and exhaust lumen. A second balloon is disposed over thefirst balloon with a thermal barrier therebetween. A plurality oftemperature sensors are affixed to the second balloon so as to providetemperature measurements of the lumen surface.

In another aspect, the present invention provides a catheter fordetecting a vulnerable plaque of a blood vessel having a lumen surface.The catheter generally comprises a catheter body having a proximal endand a distal end with a supply lumen and an exhaust lumen extendingtherebetween. A balloon is disposed on the distal end of the catheterbody in fluid communication with the supply lumen and exhaust lumen. Aplurality of temperature sensors are supported by the balloon so as toprovide temperature measurements of the lumen surface.

Optionally, an inflation supply may be in fluid communication with thesupply lumen at the proximal end of the catheter body. The inflationsupply may be configured to inflate the balloon with a gas whendetecting the vulnerable plaque. The gas in the balloon may have atemperature of about 20° C. or more during the temperature measurements.In some embodiments, the inflation supply may further be configured todirect cooling fluid to the balloon in a treatment mode so that an outertemperature of the balloon is about 10° C. or less.

In another aspect, the invention also provides a kit for treatingvulnerable plaque in a blood vessel. The kit comprises a catheter havinga proximal end, a distal end, and a cooling member near its distal end.Instructions are included in the kit for use of the catheter. Theseinstructions comprise the step of cooling the blood vessel adjacent thevulnerable plaque to inhibit release of the retained fluid into theblood vessel. Such a kit may include instructions for any of the methodsdescribed herein.

In yet another aspect, the invention provides a kit for detectingvulnerable plaque of a blood vessel. The kit comprises a catheter havinga proximal end, a distal end, and a balloon member with a plurality oftemperature sensors near its distal end. Instructions are included inthe kit for use of the catheter. These instructions comprise the stepsof positioning a balloon within the vessel lumen adjacent a plaque,inflating the balloon so that a plurality of temperature sensors affixedto the balloon are coupled to a surface of the vessel lumen, and sensinga temperature differential along the lumen surface with the sensors.Such a kit may include instructions for any of the methods describedherein.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A and 1B are cross-sectional views of a blood vessel containing amature vulnerable plaque.

FIG. 2 illustrates a cross-sectional view of a vulnerable plaque ruptureand plaque hemorrhage in the blood vessel.

FIG. 3 illustrates a cross-sectional view of a thrombotic occlusion inthe blood vessel.

FIG. 4 illustrates an exploded cross-sectional view of FIG. 1A takenalong line 4-4.

FIG. 5 illustrates an exemplary cryotherapy catheter for detecting andtreating vulnerable plaque.

FIG. 6 is a cross-sectional view of the catheter taken along line 6-6 inFIG. 5.

FIG. 7 is a functional flow diagram illustrating the operation of anautomatic fluid shutoff mechanism of the catheter of FIG. 5.

FIGS. 8A and 8B illustrate a handle and removable energy pack for use inthe cryotherapy catheter of FIG. 5.

FIG. 9 illustrates a block diagram of a circuit which measures atemperature differential of the lumen surface.

FIG. 10A illustrates an alternative catheter for detecting vulnerableplaque.

FIG. 10B is a cross-sectional view of the catheter taken along line10B-10B in FIG. 10 A.

FIGS. 11A-11C illustrate use of the catheter of FIG. 5 for treatment ofvulnerable plaque.

FIG. 12A is a graph illustrating a transition temperature which effectsa lipid core transition of the vulnerable plaque.

FIG. 12B illustrates the lipid core transition from a liquid, disorderedstate to a solid, ordered state.

FIG. 13A and 13B illustrate additional treatments in conjunction withcooling of the vulnerable plaque.

FIG. 14 illustrates a vulnerable plaque treatment kit including theapparatus of FIG. 5 and instructions for use.

FIGS. 15A and 15B are a perspective view and a cross-sectional view,respectively of hot plaque thermal models.

FIGS. 16A-16C are steady-state initial temperature distributions of thehot plaque thermal model of FIGS. 15A and 15B, a temperaturedistribution of the hot plaque thermal 30 seconds after engagement witha balloon filled by 35° C. water, and a temperature distribution of thehot plaque 30 seconds after engagement by a balloon filled with 35° C.gas, respectively.

FIGS. 17A-17D graphically represent transient measurement temperatureswith balloons having gas and liquid inflation fluids at differingtemperatures.

DESCRIPTION OF THE SPECIFIC EMBODIMENTS

As used herein, the terms “vulnerable plaque” and “hot plaque” refer toatherosclerotic plaque that is thrombosis-prone. FIGS. 1A and 1Billustrate cross-sectional views of a blood vessel 100 containing amature vulnerable plaque 102 within a lumen 104 of the vessel. Thevulnerable plaque 102 generally comprises anecrotic core 106 of soft,lipid-rich, atheromatous gruel and a fibrous, sclerotic cap 108 of acollagen matrix of smooth muscle cells that covers the core 106. Thegruel generally comprises a liquid of esterified cholesterol and lowdensity lipoproteins which is releasably retained by the vulnerableplaque 102. Disruption or Assuring of the cap 108 may cause plaquehemorrhage 110 (release of the highly thrombogenic lipid-rich liquid 106through the ruptured plaque), as seen in FIG. 2. As a result of plaquehemorrhage 110, the highly thrombogenic lipid-rich liquid 106 is exposedto flowing blood of the vessel lumen 104. As illustrated in FIG. 3,release of the thrombogenic liquid may cause a thrombotic occlusion 112(blood clot) of the entire vessel lumen, which in turn may be lead tolife-threatening conditions, such as a stroke or sudden cardiac death.

Three determinants of vulnerability are illustrated in FIG. 4, which isan exploded cross-sectional view of FIG. 1B taken along line 4-4.Susceptibility of a vulnerable plaque to rupture may be primarilydetermined from the size 114 and consistency of the athermanous core(e.g. a larger core increases chances for rupture), the thickness 116and structural integrity of the sclerotic cap (e.g. a thinner capincreases chances for rupture), and cap inflammation (e.g. macrophagefoam cell 118 infiltration weakens the cap 120 and increases chances forrupture). Additionally, vulnerable plaque disruption may be triggered bynumerous extrinsic stresses imposed on the plaque. For example,fluctuations in intraluminal blood pressure, pulse pressure, heartcontraction, vasospasm, and the like may precipitate disruption of avulnerable plaque. Alternatively, mechanical stresses caused by primarytreatments like PTA or stenting may trigger rupture as well.

Referring now to FIGS. 5 and 6, an exemplary cryotherapy catheter 10(which is more fully described in co-pending application Ser. no.09/619,583 filed Jul. 19, 2000 (Attorney Docket No. 018468-000610US)),the full disclosure of which is incorporated herein by reference) fordetecting and treating vulnerable plaque 102 of a blood vessel 100having a lumen surface 105 (see FIG. 1 A) will be described. Thecatheter 10 comprises a catheter body 12 having a proximal end 14 and adistal end 16 with a cooling fluid supply lumen 18 and an exhaust lumen20 extending therebetween. A first balloon 22 is disposed near thedistal end of the catheter body 12 in fluid communication with thesupply and exhaust lumens. A second balloon 24 is disposed over thefirst balloon 22 with a thermal barrier 26 therebetween.

The balloons 22, 24 may be an integral extension of the catheter body12, but such a structure is not required by the present invention. Theballoons 22, 24 could be formed from the same or a different material asthe catheter body 12 and, in the latter case, attached to the distal end16 of the catheter body 12 by suitable adhesives, heat welding, or thelike. The catheter body 12 may be formed from conventional materials,such as polyethylenes, pebax, polyimides, and copolymers and derivativesthereof. The balloons 22, 24 may also be formed from conventionalmaterials used for angioplasty, preferably being inelastic, such aspolyethylene terephthalate (PET), polyethylene, pebax, or other medicalgrade material suitable for constructing a strong non-distensibleballoon. Additionally, balloons 22 and 24 could be formed from differentmaterial to provide improved protection. For example, the first balloon22 could be formed from PET to provide strength while the second balloon24 could be formed from polyethylene to provide durability. The balloons22, 24 have a length of at least 1 cm each, more preferably in the rangefrom 2 cm to 5 cm each. The balloons 22, 24 will have diameters in therange from 2 mm to 5 mm each in a coronary artery and 2 mm to 10 mm eachin a peripheral artery.

The thermal barrier 26 may comprise a gap maintained between theballoons 22, 24 by a filament. The filament typically comprises ahelically wound, braided, woven, or knotted monofilament. Themonofilament may be formed from PET or polyethylene napthlate (PEN), andaffixed to the first balloon 22 by adhesion bonding, heat welding,fasteners, or the like. The thermal barrier 26 may also comprise a gapmaintained between the balloons 22, 24 by a plurality of bumps on anouter surface of the first balloon 22 and/or an inner surface of thesecond balloon 24. The plurality of bumps may be formed in a variety ofways. For example, the bumps may be intrinsic to the balloon (createdduring balloon blowing), or the bumps could be created by deforming thematerial of the balloon wall, by affixing mechanical “dots” to theballoon using adhesion bonding, heat welding, fasteners, or the like.Alternatively, the thermal barrier 26 may comprise a gap maintainedbetween the balloons 22, 24 by a sleeve. The sleeve may be perforatedand formed from PET or rubbers such as silicone and polyurathane. Stillfurther structures might be employed to maintain a gap between theballoons, including a liquid.

Hubs 34 and 36 are secured to the proximal end 14 of the catheter body12. Hub 34 provides a port 38 for connecting a cryogenic fluid source tothe fluid supply lumen 18 which is in turn in fluid communication withthe inner surface of the first balloon 22. Hub 34 further provides aport 40 for exhausting the cryogenic fluid which travels from balloon 22in a proximal direction through the exhaust lumen 20. Hub 36 provides aport 42 for a guidewire which extends through a guidewire lumen 44 inthe catheter body 12. Typically, the guidewire lumen 44 will extendthrough the exhaust lumen 20, as shown in FIG. 6. The guidewire lumen 44may also extend axially outside the exhaust lumen 20 to minimize theoccurrence of cryogenic fluid entering the blood stream via theguidewire lumen 44. Optionally, the guidewire lumen 44 may extendoutside the inner surface of the first balloon 22 or the guidewire lumen44 may allow for a guidewire to extend outside both balloons 22, 24.Additionally, a reinforcing coil 46 may extend along the catheter body12 proximal the first balloon 22. The reinforcing coil 46 may comprise asimple spring having a length typically in the range from 6 cm to 10 cmto prevent the catheter 10 from kinking up inside the blood vessel.

The cryotherapy catheter 10 in FIG. 5 additionally illustrates a safetymechanism that monitors the containment of the first and second balloons22, 24. The first balloon 22 defines a volume in fluid communicationwith the supply and exhaust lumens. A fluid shutoff is coupled to acryogenic fluid supply with the supply lumen 18. The second balloon 24is disposed over the first balloon 22 with a vacuum space 52therebetween. The vacuum space 52 is coupled to the fluid shutoff so asto inhibit flow of cryogenic fluid into the first balloon 22 in responseto a change in the vacuum space 52.

FIG. 7 illustrates a functional flow diagram of the automatic fluidshutoff mechanism 54. The fluid shutoff 54 typically comprises a vacuumswitch 56 connected to a shutoff valve 58 by a circuit, the circuitbeing powered by a battery 60. The switch 56 may remain closed only whena predetermined level of vacuum space 52 is detected in the secondballoon 24. The closed switch 56 allows the shutoff valve 58, in fluidcommunication with the cryogenic fluid supply 62, to be open.Alternatively, the circuit may be arranged so that the switch 56 is openonly when the predetermined vacuum space 52 is present, with the shutoffvalve 58 being open when the switch is open. The vacuum space 52 isreduced when either the first balloon 22 is punctured, allowingcryogenic fluid to enter the vacuum space 52, or the second balloon 24is punctured, allowing blood to enter the vacuum space 52. In additionto monitoring the containment of both balloons 22, 24, in the event of afailure, the vacuum switch 56 will be triggered to prevent the deliveryof additional cryogenic fluid from the fluid supply 62 into the supplylumen 18. The second balloon 24 also acts to contain any cryogenic fluidthat may have escaped the first balloon 22.

The vacuum space 52 may be provided by a simple fixed vacuum chamber 64coupled to the vacuum space 52 by a vacuum lumen 66 of the body 12 via avacuum port 68 (See FIG. 5). In the exemplary embodiment, a positivedisplacement pump (ideally being similar to a syringe) is disposedwithin handle 74 and may be actuated by actuator 75, as seen in FIG. 8A.The vacuum space 52 should comprise a small volume of vacuum in therange from 1 mL to 100 mL, preferably 10 mL or less, as a smaller vacuumspace 52 facilitates detection of a change in the amount of vacuum whena small amount of fluid leakage occurs. The cryogenic fluid supply 62and battery 60 for powering the circuit may be packaged together in anenergy pack 70, as seen in FIG. 8B. The energy pack 70 is detachablefrom a proximal handle 74 of the catheter body and disposable. Aplurality of separate replaceable energy packs 70 allow for multiplecryogenic cooling cycles. Alternative fluid supply and batterystructures might also be employed, including those described in U.S.patent application Ser. No. 09/953464, filed on Sep. 14, 2001 andassigned to the assignee of the present application, the full disclosureof which is incorporated herein by reference.

An audio alert or buzzer 76 may be located on the handle 74, with thebuzzer providing an audio warning unless the handle is maintainedsufficiently upright to allow flow from the fluid supply 62. Thecryotherapy catheter may additionally comprise a hypsometer 72 coupledto the volume by a thermistor, thermocouple, or the like located in thefirst balloon 22 or handle to determine the pressure and/or temperatureof fluid in the first balloon 22. The hypsometer allows for accuratereal time measurements of variables (pressure, temperature) that effectthe efficacy and safety of cryotherapy treatments.

The dual balloon cryotherapy catheter 10 in FIG. 5 also illustrates atemperature sensing mechanism that provides for thermographic detectionof vulnerable plaque. A plurality of temperature sensors 78 are affixedto the second balloon 24 so as to provide direct temperaturemeasurements of the lumen surface 105 (see FIG. 1A). The temperaturesensors 78 may comprise a plurality of up to 20 thermocouples orthermistors and may be capable of detecting temperature differencesgreater than 0.1° C. Alternative temperature sensors might also beemployed including a fiber optic cable connected to an infrareddetector, resistance temperature detectors, or the like. The temperaturesensors 78 may be secured to the second balloon 24 at a series of axialand circumferential locations. The plurality of temperature sensors 78may be affixed by adhesion bonding, heat welding, fasteners, or the liketo an outer surface of the second balloon 24, as shown in FIG. 5, or maybe alternatively affixed to an inner surface of the second balloon 24.Still further alternatives are also possible, including attaching thesensors to, impregnating the sensors in, and/or forming the sensors onan insulation layer or other material disposed between the balloons.Temperature sensor wires 80 may be secured along the length of thecatheter shaft 12 within a thin sleeve 82 formed from PET or rubberssuch as silicone and polyurathane, or in the latter case the wires 80may be threaded through the vacuum lumen 66. A connector 84 at theproximal end 14 of the catheter 10 may also be provided to connect thetemperature sensor wires 80 to a temperature readout device fortemperature mapping along the lumen surface. Additionally, a circuit 77may be attached to the connector 84 for measuring a temperaturedifferential AT along the lumen surface from temperature measurement T1and T2 sensed by the temperature sensors 78, as illustrated in the blockdiagram of FIG. 9. An indicator which is triggered above a thresholdtemperature differential may also be located on the connector. Anindicator signal indicating a temperature above a threshold temperaturedifferential may optionally be used as a trigger to initiate treatmentof the vulnerable plaque, with or without further input from thephysician. Hence, the system may first diagnose a plaque as a hotplaque, optionally by inflating the balloon with a warm gas, and thenautomatically treat that hot plaque by inflating the balloon so as to(usually cryogenically) cool the hot plaque.

Detection of vulnerable plaque may be carried out by introducing thecryotherapy catheter 10 into a lumen 104 of the blood vessel 100 over aguidewire. The first balloon 22 is positioned within the blood vessellumen 104 adjacent a plaque. The first balloon 22 is inflated so thatthe plurality of temperature sensors 78 affixed to the second balloon 24(which expands upon inflation) thermally couple a surface of the vessellumen. A temperature differential along the lumen surface 105 is sensedwith the sensors. Inflation of balloon 22 may be effected by a gas, suchas carbon dioxide, nitrous oxide, or the like, at a pressure in therange from about 5 psi to 50 psi. As used herein, “psi” encompassespounds per square inch above ambient pressure, sometimes referred to as“psig.” The balloon 22 will typically be inflated for a time period inthe range from 10 to 120 seconds. The balloon catheter may sense for atemperature differential in a static position or as it moving along thelumen surface. Advantageously, temperature sensors 78 thermally engagethe lumen surface to allow for direct temperature measurements to bemade at specific locations along the lumen surface. This increasedtemperature sensitivity may in turn lead to improved temperature mappingand accurate vulnerable plaque detections. Cryotherapy catheter 10 maythen be used for treating the detected vulnerable plaque as described inmore detail below with reference to FIGS. 11A-11C.

An alternative catheter 10′ for detecting a vulnerable plaque of a bloodvessel having a lumen surface is illustrated in FIGS. 10A and 10B.Detection catheter 10′ comprises a catheter body 12 having a proximalend 14 and a distal end 16 with a supply lumen 88 and an exhaust lumen88 extending therebetween. A balloon 86 is disposed on the distal end ofthe catheter body 12. Balloon 86 has an inner surface in fluidcommunication with the supply lumen and exhaust lumen. A plurality oftemperature sensors 78 are affixed to an outer surface of the balloon 86so as to provide direct temperature measurements of the lumen surface105 (see FIG. 1A).

Detection of vulnerable plaque may be carried out by introducing thedetection catheter 10′ into a lumen 104 of the blood vessel 100 over aguidewire. The balloon 86 is positioned within the vessel lumen adjacenta plaque. The balloon 86 is inflated so that a plurality of temperaturesensors 78 affixed to the balloon thermally couple a surface of thevessel lumen. A temperature differential along the lumen surface issensed with the sensors. Balloon 86 is generally inflatable withstandard inflation media, such as contrast, saline, or the like. Aninflation media supply and/or exhaust port 90 is connected to the supplyand/or exhaust lumen 88 which is in turn in fluid communication with theinner surface of balloon 86. Balloon 86 will typically be inflated for atime period in the range from 10 to 120 seconds. The balloon cathetermay sense for a temperature differential in a static position or as itmoving along the lumen surface.

Referring now to FIGS. 11A through 11C, use of cryotherapy catheter 10of FIG. 5 for treatment of vulnerable plaque 102 will be described. Asillustrated in FIG. 11A and 11B, catheter 10 will be introduced into alumen 104 of the blood vessel 100 over a guidewire GW. The first balloon22 is positioned within the blood vessel lumen 104 adjacent thevulnerable plaque 102. Cryogenic cooling fluid is introduced into thefirst balloon 22 (in which it often vaporizes) and exhausted. The secondballoon 24 expands to radially engage the vessel wall, as illustrated byFIG. 11C. The vaporized fluid serves both to inflate balloon 22 (andexpand balloon 24) and to cool the exterior surface of the balloons 22,24. The blood vessel 100 adjacent the vulnerable plaque 102 is cooled toa temperature sufficient to inhibit release of retained fluid 106 fromwithin the vulnerable plaque 102 into the blood vessel 100. The coolingtreatment will be directed at all or a portion of a circumferentialsurface the vessel lumen. Preferably cooling will inhibit release oflipid-rich liquid being releasably retained by the vulnerable plaque bystabilizing the lipid-rich liquid 106 to a lipid-rich solid or gel 106′(which is described in more detail in FIGS. 12A-12B below). Heattransfer will also be inhibited between the first and second balloons22, 24 by the thermal barrier 26 so as to limit cooling of thevulnerable plaque to a desired temperature profile. Additionally,containment of the first and second balloons 22, 24 will be monitoredduring cooling by the fluid shutoff mechanism (see FIG. 7).

Suitable cryogenic fluids will preferably be non-toxic and may includeliquid nitrous oxide, liquid carbon dioxide, cooled saline and the like.The cryogenic fluid will flow through the supply lumen 18 as a liquid atan elevated pressure and will vaporize at a lower pressure within thefirst balloon 22. For nitrous oxide, a delivery pressure within thesupply lumen 18 will typically be in the range from 600 psi to 1000 psiat a temperature below the associated boiling point. After vaporization,the nitrous oxide gas within the first balloon 22 near its center mayhave a pressure in the range from 15 psi to 100 psi, optionally having apressure in a range from 50 to 150 psi. The nitrous oxide gas may have apressure in the range from 50 psi to 100 psi in a peripheral artery,preferably having a pressure in a range from 100 to 150 in a peripheralartery, and may have a pressure in a range from about 15 psi to 45 psiin a coronary artery, preferably having a pressure in a range from 100to 150 psi in a coronary artery.

The temperature of an inside surface of the first balloon may be in therange from about −55° C. to −75° C. (preferably being in a range fromabout −30 C to −50 C) and an outside surface of the first balloon may bein the range from about −25° C. to −45° C. (preferably being in a rangefrom about −20 C to −40 C). The temperature of an outside surface of thesecond balloon will be in the range from about 10° C. to −40° C.,preferably from about 10° C. to −20° C., more preferably from about 5°C. to −10° C. This will provide a desired treatment temperature in arange from about 10° C. to −40° C., preferably from about 10° C. to −20°C., more preferably from about 5° C. to −10° C. The tissue is typicallymaintained at the desired temperature for a time period in the rangefrom about 15 to 120 seconds, optionally being from 30 to 60 seconds,preferably being from 20 to 60 seconds.

Vulnerable plaque stabilization may be enhanced by repeating cooling incycles, typically with from about 1 to 3 cycles, with the cycles beingrepeated at a rate of about one cycle every 120 seconds.

In some instances, cooling of the vessel may be limited to inhibit oravoid necrosis and/or apoptosis of tissue adjacent the lipid-richliquid, particularly of the tissues defining a cap of cells 108 betweenthe lipid-rich liquid 106 and the lumen of the blood vessel 104 (seeFIG. 1 A). Apoptosis or cell necrosis may be undesirable if it weakensthe cap of cells as cap weakening may likely incite rupture of thevulnerable plaque and release of the lipid-rich liquid. Thus, thepresent invention may inhibit release of the retained fluid into theblood vessel without affecting the viability of the cap cells 108 andother cells which line the body lumen.

In other applications, cooling of the vessel at cooler temperatures maybe desirable to provide for or induce apoptosis and/or programmed celldeath stimulation of inflammatory cells (e.g. macrophages 118, see FIG.4) in the vulnerable plaque 102. Apoptosis may be desirable as thepresence of such inflammatory cells may trigger cap weakening or erosionwhich in turn may lead to vulnerable plaque release of the lipid-richliquid. Cooling at temperatures in the range from about 0° C. to −15° C.may inhibit inflammation and deterioration of the vulnerable plaque,particularly of the tissues defining the cap of cells 108.Alternatively, it may be beneficial to provide for or induce necrosis inthe cap cells 108 at cooling temperatures below about −20° C. Capnecrosis may stimulate cellular proliferation and thickening of the capwhich in turn may inhibit cap rupture.

Referring now to FIGS. 12A and 12B, transition of the vulnerableplaque's lipid-rich liquid core 106 will be described. FIG. 12Aillustrates the transition temperature which effects a lipid coretransition. The main transition point 122 occurs at some point betweenthe transition temperature range of 10° C. to −10° C. At this transitionpoint 122, the lipid core may undergo a phase change from a disorderedcrystalline state fluid 106 to a ordered crystalline state solid or gel106′, as shown in FIG. 12B. Thus, vulnerable plaque can be stabilized bycooling the lipid-rich liquid core 106 sufficiently to change its state,typically from a disordered lipid to a highly ordered hexagonal lattice.Advantageously, a transition temperature above −5° C. also inhibitsnecrosis and/or apoptosis of tissue adjacent the lipid-rich liquid 106,particularly of the cap 108.

With reference now to FIGS. 13A and 13B, additional treatments inconjunction with cooling of the vulnerable plaque will be illustrated.FIG. 13 A illustrates a cross section of a blood vessel 100 that hasbeen cooled so that the vulnerable plaque has been stabilized tolipid-rich solid/gel 106′. A stent 124 has been placed within the vessellumen while the plaque is stabilized to provide a long-term restraint oflipid-rich fluid 106, and possibly to provide a structural scaffoldingfor healthy endothelial cells via tissue ingrowth. The stent may alsoalleviate plaque-induced stenosis and to improve the patency of thelumen. Other suitable primary treatments of the stabilized plaque mayinclude balloon angioplasty, atherectomy, rotational atherectomy, laserangioplasty, or the like, where the lumen of the treated blood vessel isenlarged to at least partially alleviate a stenotic condition. In thecase of arteries, the primary treatment will be effected shortly before,during, or preferably very shortly after the cooling treatment,preferably within 60 seconds of the cooling treatment, more preferablyimmediately following the cooling of the lipid-rich liquid to a desiredtemperature. In some instances, cooling may effect passivation of thevulnerable plaque, possibly reducing a size of the lipid-rich liquid106″, as illustrated in FIG. 13B, or modifying a cellular consistency orcomposition of the lipid-rich liquid, and/or the like by altering thechemistry or life cycle of the vulnerable plaque. Passivation may alsoinclude enhancing a structural integrity of cap 108 (e.g. increasing thethickness, strength, elasticity, or hardness of the cap), modifying acellular composition or property of the cap, and/or the like via scarformation or alteration of the chemistry of the vulnerable plaque.

A kit 126 including a catheter 10 and instructions for use 128 isillustrated in FIG. 14. Catheter 10 may comprise the dual ballooncatheter of FIG. 5, as illustrated in FIG. 14, or a catheter having aproximal end, a distal end, and a cooling member near its distal end.Instructions for use 128 may describe any of the associated method stepsset forth above for detection and/or treatment of vulnerable plaque.Instructions for use 128 will often be printed, optionally appearing atleast in part on a sterile package 130 for balloon catheter 10. Inalternative embodiments, instructions for use 128 may comprise a machinereadable code, digital or analog data graphically illustrating ordemonstrating the use of balloon catheter 10 to detect and/or treatvulnerable plaque. Still further alternatives are possible, includingprinting of the instructions for use on packaging 132 of kit 126, andthe like.

Referring now to FIGS. 15A and 15B, a thermal model 200 was developed tostudy heat transfer from a volume of hot plaque 202. Hot plaque 202 wasassumed to be a cylinder having a diameter of 2 mm and a length of 2 mm.A circumferential surface 204 and a first end surface 206 of hot plaque202 are thermally coupled to normal tissue at 37° C. A second end 208 ofhot plaque 202 defines a portion of a luminal wall, and is thermallyexposed directly to blood flow within the lumen of a blood vessel, orindirectly to a fluid within a balloon through a balloon wall (see FIG.15B). Given the assumed cylindrical shape of hot plaque 202, the hotplaque (and its thermal characteristics) are radially symmetrical abouta center line CL. Hence, the illustration shown in FIG. 15B (andsubsequent graphs of temperature distribution within hot plaque 202) areillustrated as a radial cross-section beginning at the center line CLand ending at circumferential surface 204.

Heat transfer coefficients for thermal flows between hot plaque 202 andsurrounding tissues can be modeled using known thermal properties of thetissue and/or by measuring the properties of appropriate human, animalor model tissues. Similarly, heat flow through luminal surface end 208of hot plaque 202 may be based on known or measured heat transferproperties. The thermal model results described below make use of a heattransfer coefficient directly between a hot plaque surface 208 and ablood flow 210 within the lumen of 0.000594 W/mm²−° C.

Referring now to FIGS. 15A and 16A, the internal metabolic heating rateto achieve an average hot plaque luminal surface temperature of 38° C.may be determined based on thermal model 200. The 38° C. average hotplaque luminal surface temperature is based on published hot plaquecharacteristics. As illustrated in FIG. 16A, the steady state internaltemperature distribution is hottest at the core of hot plaque 202 due toheat removal from the circumferential surface 204, the tissue engagingend 206, and the luminal surface 208. Hot plaque luminal surfacetemperatures may be measured using a thermocouple, a fiber optic cableconnected to an infrared detector, resistance temperature detectors, orthe like.

Referring now to FIGS. 15B and 16B and C, once the metabolic heatingrate of hot plaque 202 has been identified using thermal model 200, thethermal model may be modified to include one or more balloon wallsdisposed between luminal surface 208 and a balloon inflation fluid 210.In the exemplary thermal model, the luminal hot plaque surface 208 wasassumed to be covered by first and second layers of PET 212, 214. Eachlayer was modeled as having a thickness of 0.0075 mm. Clearly,alternative single or multiple layer balloon structures might also bemodeled by changing the thermal properties, thicknesses, or materials ofthe layers disposed between the hot plaque and the balloon inflationfluid.

The fluid 210 of the thermal model 200 within the balloon was assumed tobe water or nitrous oxide gas. Temperatures were assumed to be measuredat a temperature sensor 216 disposed between balloon layers 212, 214,with the exemplary temperature sensor location being disposed at aradius of 0.583 mm from the hot plaque center so as to result in astarting surface temperature of approximately 38° C. Temperature of thetemperature sensor versus time was determined (see FIGS. 17A-D) andinternal and surface temperature distributions were computed after 30seconds of thermal exposure.

Referring now to FIGS. 16A-C, FIG. 16A graphically illustratessteady-state temperature distribution within the hot plaque prior toengagement by the balloon wall, thereby providing an initial temperatureprofile. FIG. 16B illustrates the hot plaque temperature distribution 30seconds after thermal engagement by a balloon filled with 35° C. water.FIG. 16C shows hot plaque internal temperature distribution 30 secondsafter exposure to a balloon filled with gas at 35° C. Qualitatively, itcan be seen that the gas-filled balloon provides a temperaturedifferential amplification along luminal tissue surface 208, as comparedto the water-filled balloon. The region of the luminal wall having ameasurably higher temperature is also larger for the gas-filled balloonthan for the water-filled balloon, facilitating identification andlocating of the hot plaque.

Referring now to FIGS. 17A-D, transient thermal analyses were made usingthe initial temperature distribution shown in FIG. 16A. Similar thermalanalyses were performed for a tissue surface of a normal plaque, whichis presumed to have a uniform temperature of 37° C. throughout.Transient tissue temperatures measured by a thermocouple 216 disposedbetween layers of a balloon 212, 214 are compared in FIG. 17A, with thegraph illustrating measurement site temperatures times after engagementat a range of between a balloon filled with 37° C. gas or water at anormal tissue site and at a hot tissue (also referred to as a hot plaqueor vulnerable plaque) site.

As would be expected, when a normal tissue site (having an initialtemperature of 37° C.) is engaged by a balloon filled with water ornitrous oxide gas at 37° C., the temperature sensors indicates aconstant 37° C. When a hot plaque is engaged with a water-filledballoon, the temperature sensor indicates an increasing temperature.While the initial surface of the hot plaque was 38° C., the reading fromthe water-filled balloon in FIG. 17A remains significantly less than 38°C., due to the heat transfer through the layers of the balloon wall toand from the water. As the heat transfers between the balloon wall andan internal gas is significantly less than that of a water-filledballoon, the hot tissue site as measured by a gas-filled balloonindicates a temperature difference of more than one degree between thehot tissue site and the normal tissue site. The gas-filled balloon actsas a thermal insulator on the hot tissue surface, allowing the measuredtemperature to rise beyond the initial hot tissue temperature. Thissurprising result can be understood with reference to FIGS. 16A, and theabove description of the thermal model of the hot plaque, once themetabolic heating (and associated cooling by the luminal blood flow) isconsidered. Hence, once a gas-filled balloon engages the hot plaquesurface, the metabolic heating within the hot plaque and the insulatingproperties of the gas-filled balloon cause a signal amplification of thehot plaque indicating temperature differential.

Referring now to FIGS. 17B, C, and D, the transient temperature responsefor balloons inflated with gases and liquids at temperatures of 35° C.,30° C., and 25° C., respectively, are provided. These figures indicatethat the surface temperature differences between hot plaque and normalluminal tissues, as measured along the balloon wall, are approximatelytwice as large with a gas-filled balloon as they are with aliquid-filled balloon. Additionally, the maximum hot plaque surfacetemperature is generally greater with a gas-filled balloon than with aliquid-filled balloon, and the use of a gas-filled balloon actuallyamplifies the hot plaque surface temperature differential when theinitial gas temperature is 30° C. or higher. Once again, this signalamplification results from the reduced heat transfer from the hot plaqueinto a gas-filled balloon as compared to the heat transfer to luminalblood flow and/or a liquid-filled balloon. This amplifying effect is notprovided with a liquid-filled balloon.

In general, thermal model 200 indicates a greater different between hotplaque luminal surface temperatures and normal plaque or healthy luminalsurface tissue temperatures after balloon inflation. A larger differencein these temperatures can result in a higher detection sensitivity. Theabsolute value of the surface temperature after balloon inflation wasalso evaluated, as higher surface temperatures also produce a higherdifferentiation sensitivity. Per both of these evaluation criteria, thegas-filled balloon performance exceeded that of the liquid-filledballoon performance particularly when relatively warm gases were usedwithin the balloon. Specifically, under the thermal model analyses, thegas-filled balloon resulted in a higher difference between the measuredhot plaque surface temperature and the measured normal plaque surfacetemperature, with the temperature differences using a gas-filled balloonbeing approximately twice those resulting from a liquid-filled balloon.Additionally, the absolute measured hot plaque surface temperature wasuniformly higher when a gas-filled balloon was modeled as compared to awater-filled balloon.

While the above is a complete description of the preferred embodimentsof the invention, various alternatives, modifications, and equivalentswill be obvious to those of skill in the art. Hence, the abovedescription should not be taken as limiting the scope of the inventionwhich is defined by the appended claims.

1. A catheter system comprising: a catheter shaft including a proximalregion and a distal region, the catheter shaft defining a supply lumen;a first balloon disposed about the distal region of the catheter shaftand having a wall with an outer surface and an inner surface, whereinthe inner surface defines a first cavity that is in fluid communicationwith the supply lumen; a second balloon disposed over the first balloonand defining a thermal barrier therebetween; an inflation supply influid communication with the supply lumen of the catheter shaft, whereinthe inflation supply is configured to provide a fluid to the firstcavity for expanding the first balloon; and a plurality of temperaturesensors coupled to the second balloon so as to provide temperaturemeasurements.
 2. The catheter system of claim 1, further comprisingexternal equipment comprising a circuit and an indicator that providesan indication to a user of the catheter system, the circuit adapted tomeasure a temperature differential between at least two different onesof the plurality of temperature sensors, and to generate a signal on theindicator when the temperature differential is greater than a threshold.3. The catheter system of claim 1, wherein the inflation supply isfurther configured to direct cooling fluid to the first balloon in atreatment mode so that an outer temperature of the second balloon isabout 10° C. or less.
 4. The catheter system of claim 1, wherein theplurality of temperature sensors are coupled to an outer surface of thesecond balloon.
 5. The catheter system of claim 4, wherein the pluralityof temperature sensors provide direct temperature measurements of thelumen surface.
 6. The catheter system of claim 1, wherein the pluralityof temperature sensors are disposed between the first balloon and thesecond balloon.
 7. The catheter system of claim 1, wherein the pluralityof temperature sensors comprise thermocouples or thermistors.
 8. Thecatheter system of claim 1, wherein the plurality of temperature sensorsare distributed circumferentially about the second balloon.
 9. Thecatheter system of claim 2, wherein the external equipment furthercomprises a connector and a temperature readout device connectable tothe connector.
 10. The catheter system of claim 9, wherein the circuitis attached to the connector.
 11. The catheter system of claim 1,wherein the fluid has a temperature of about 30° C. or more.
 12. Acatheter system, comprising: a catheter body having a proximal end and adistal end with a supply lumen extending therebetween; a balloondisposed about the distal end of the catheter body, the balloon in fluidcommunication with the supply lumen, the balloon having a balloon wallwith an outer surface and an inner surface, the outer surface of theballoon wall being an outer surface of the catheter and the innersurface defining an inflation cavity; an inflation supply in fluidcommunication with the supply lumen at the proximal end of the catheterbody, the inflation supply configured to inflate the balloon inflationcavity with a gas; a gas disposed in the balloon inflation cavity; aplurality of temperature sensors affixed to the balloon wall so as toprovide temperature measurements of the lumen surface; and a deviceadapted to measure a temperature differential between at least twodifferent ones of the plurality of temperature sensors.
 13. The cathetersystem of claim 12, wherein the inflation supply is further configuredto direct cooling fluid to the balloon in a treatment mode so that anouter temperature of the balloon is about 10° C. or less.
 14. Thecatheter system of claim 12, wherein the plurality of temperaturesensors are affixed to an outer surface of the balloon.
 15. The cathetersystem of claim 14, wherein the plurality of temperature sensors providedirect temperature measurements of the lumen surface.
 16. The cathetersystem of claim 12, wherein the balloon comprises a first balloon andfurther comprising a second balloon disposed over the first balloon,wherein the plurality of temperature sensors are disposed between thefirst balloon and the second balloon.
 17. The catheter system of claim12, wherein the plurality of temperature sensors are distributedcircumferentially about the balloon.
 18. The catheter system of claim12, wherein the device further comprises a connector and a temperaturereadout device connectable to the connector.
 19. The catheter system ofclaim 10, wherein the indicator is located on the connector.
 20. Acatheter system, comprising: a catheter shaft including a proximalregion and a distal region, the catheter shaft defining a supply lumen;a first balloon disposed about the distal region of the catheter shaftand having a wall with an outer surface and an inner surface, whereinthe inner surface defines a first cavity that is in fluid communicationwith the supply lumen; a second balloon disposed over the first balloon,wherein one or more members are disposed between the first balloon andthe second balloon to define a thermal barrier between the first balloonand the second balloon; an inflation supply in fluid communication withthe supply lumen of the catheter shaft, wherein the inflation supply isconfigured to provide a fluid to the first cavity for expanding thefirst balloon; and a plurality of temperature sensors coupled to thesecond balloon so as to provide temperature measurements.